Current treatment for human cutaneous leishmaniasis (CL) relies on pentavalent antimonials. Although efficacy of these drugs is high (around 85%), their widely documented toxicity and increasing resistance makes the search for therapeutic alternatives a priority for endemic countries. To evaluate the efficacy and tolerability of the pentamidine isethionate for the treatment of cutaneous leishmaniasis caused by L. (V) panamensis in a pilot clinical trial. Sixty three individuals suffering CL were enrolled. Patients received four intramuscular injections of pentamidine (4 mg/Kg/injection) administered every other day, and both clinical efficacy and side effects were documented during the following 6 months. Of the 63 patients enrolled, 43 could be followed for 6 months. 86% (37/43) of treated patients healed all their lesions by 1.5 months after therapy. Treatment failure was observed in only five patients (11.6%; 5/43). One patient showed relapse. Overall tolerance of treatment was good, with adverse events such as local pain and swelling at the site of injection, dizziness and fever, varying from mild to moderate. Hypoglycemia, hypotension or diabetes were not observed. These results confirm the previously reported efficacy of pentamidine for the treatment of CL in Colombia and Brazil, and, additionally, highlight the low intensity and frequency of side effects in a civilian population. No serious adverse events were recorded.